Method for manufacturing novel hollow particles

Abstract

A method for manufacturing a hollow particle is provided. The method comprises the steps of (a) providing a hollow particulate; (b) soaking the hollow particulate in an amine solution to form amine groups on the surface of the hollow particulate; (c) adding a polypeptide, and the polypeptide is linked to the amine groups on the surface of the hollow particulate; and (d) adding a target molecule, and the target molecule is bound to the amine group which are still not bound.

What is claimed is: 
     
       1. A method for manufacturing a hollow particle comprises:
 (1) providing a hollow particulate; 
 (2) soaking the hollow particulate in an amine solution to form amine groups on the surface of the hollow particulate; 
 (3) adding a polypeptide, and the polypeptide is linked to the amine groups on the surface of the hollow particulate; and 
 (4) adding a target molecule, and the target molecule is bound to the amine group which is still not bound to the polypeptide; 
 wherein the hollow particulate is formed by homogenizing the hollow particulate at a speed; 
 wherein the speed is lower than 1000 rpm; 
 wherein the concentration of the target molecule of the step (4) is between 0.25˜0.38 wt %. 
 
     
     
       2. The method according of  claim 1 , wherein the step (1) of the hollow particulate comprises:
 (a) providing a biodegradable material, wherein the biodegradable material dissolved in methylene chloride solution is mixed with ddH 2 O, and then homogeneous mixed to conduct the first emulsification; 
 (b) providing a PVA solution and the concentration of the PVA solution is greater than 0.5% v/v; 
 (c) cooling the PVA solution with the temperature of 10˜15° C., then stirring the PVA solution with the speed below the 1000 rpm; 
 (d) dropping slowly of the biodegradable material into the PVA solution and causing the second emulsification and forming the hollow particulate; and 
 (e) lyophilizing the hollow particulate. 
 
     
     
       3. The method according to  claim 2 , wherein the biodegradable material is select from the group consist of the polylactic acid, poly(butylene succinate), poly(butylene succinate-co-butylene adipate), poly(butylene adipate-co-terephthalamide carboxylate), polyglycolic acid, poly(lactic acid-co-glycolic acid), polycaprolactone, polyvinyl alcohol, and the mixtures thereof. 
     
     
       4. The method according of  claim 2 , wherein the PVA solution of the step (b) concentration is 1% v/v. 
     
     
       5. The method according of  claim 1 , wherein the amine solution of the step (2) is selected from the group consisting of the Hexamethylene diamine, glycine, adipicdihydrazide (ADH), PEG amination solution, NH2-PEG-NHS and NH2-PEG-NH2's DMSO solution. 
     
     
       6. The method according of  claim 1 , wherein the polypeptide of the step (3) is pretreated with an active buffer to activate a carboxyl group. 
     
     
       7. The method according of  claim 6 , wherein the active buffer includes MES buffers, EDC solution or NHS solution. 
     
     
       8. The method according of  claim 6 , wherein the pH value of the active buffer is between 5˜6. 
     
     
       9. The method according of  claim 1 , wherein the polypeptide of the step (3) is select from the group consist of the IKVAV, RGD, YIGSR, REDV, DGEA, VGVAPG, GRGDS, LDV, RGDV, PDSGR, RYWLPR, LGTIPG, LAG, RGDS, RGDF, HHLGGALQAGDV, VTCG, SDGD, GREDVY, GRGDY, GRGDSP, VAPG, GGGGRGDSP, GGGGRGDY, FTLCFD, Poly-Lysine and MAX-1;
 wherein A means (Alanine), F means (Phenylalanine), C means (Cysteine), U means (Selenocysteine), D means (Aspartic acid/Aspartate), N means (Asparagine), E means (Glutamic acid/Glutamate), Q means (Glutamine), G means (Glycine), H means (Histidine), L means (Leucine), I means (Isoleucine), K means (Lysine), O means (Pyrrolysine), M means (Methionine), P means (Proline), R means (Arginine), S means (Serine), T means (Threonine), V means (Valine), W means (Tryptophan), and Y means (Tyrosine). 
 
     
     
       10. The method according of  claim 1 , wherein the target molecule of the step (4) is selected from the group consisting of the Hyaluronic acid, Hyaluronic acid oxidation, Colleagen, Glucocorticoid, Galectin and osteopontin. 
     
     
       11. The method according of  claim 1 , wherein in the step (4), the weight ratio of the target molecule and the hollow particulate is between 1:1.5 to 1:1.